LEONARDO GOMES DA FONSECA
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
11 resultados
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- Early variation of inflammatory indexes refines prognostic prediction in patients with hepatocellular carcinoma under systemic treatment(2023) FONSECA, Leonardo G. Da; URATANI, Lucas Fernando; SOARES, Gabriella Fernandes; AMARAL, Paulo Siqueira Do; ALENCAR, Regiane Saraiva De Souza Melo; CHAGAS, Aline Lopes; ALVES, Venancio Avancini Ferreira; CARRILHO, Flair JosePrognostic markers in advanced hepatocellular carcinoma (HCC) are relevant for clinical decisions. Variations in inflammatory indexes, such as neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR), may correlate with outcomes. In the present study, it was aimed to assess the prognostic role of inflammation indexes in patients with HCC and the evolutionary behavior of these variables within the first month of treatment in a cohort of patients treated with sorafenib from 2009-2021. Subgroups were divided based on the median of each variable ('low' or 'high)'. Survival was estimated using the Kaplan-Meier method. Hazard Ratio (HR) with 95% confidence interval (CI) were estimated using Cox regression models. A total of 373 patients were included, most Child-Pugh-A (83.1%) and BCLC-C (74%). Child-Pugh-A (P=0.011), performance status 0 (P<0.001), no ascites (P<0.001) and NLR<2.6 (P<0.001) were independently associated with improved survival. Baseline PLR was not correlated with survival (P=0.137). Patients who maintained low NLR at baseline and at 1 month (reference subgroup) had improved survival (18.6 months, 95% CI:15.4-22.0) compared with the subgroup that maintained high NLR at baseline and at 1 month (4.2 months, 95% CI:3.6-5.9), with HR: 3.80 (95% CI: 2.89-4.96). The subgroup with low NLR at baseline and high NLR at 1 month had a worse prognosis compared with the reference group (HR:1.4, 95% CI: 1.1-2.0), whereas the subgroup with high NLR at baseline and low at 1 month had similar outcome (HR:1.2, 95% CI: 0.8-1.6). It was concluded that evolutionary variation of NLR has a prognostic role in HCC patients under systemic therapy. This finding suggested that systemic inflammation and early modulation of the immune environment during treatment may correlate with outcomes.
- Increasing alternatives in systemic treatment for hepatocellular carcinoma: Will algorithms be understandable?(2020) FONSECA, Leonardo G. Da; FORNER, Alejandro
- Safety and efficacy of sorafenib in patients with Child-Pugh B advanced hepatocellular carcinoma(2015) FONSECA, Leonardo Gomes Da; BARROSO-SOUSA, Romualdo; BENTO, Afonso Da Silva Alves; BLANCO, Bruna Paccola; VALENTE, Gabriel Luis; PFIFFER, Tulio Eduardo Flesch; HOFF, Paulo Marcelo; SABBAGA, JorgeSorafenib demonstrated a survival benefit in the treatment of advanced hepatocellular carcinoma (HCC) in phase III trials. However, almost all the patients included in those trials exhibited well-preserved liver function (Child-Pugh A). The aim of this study was to describe our experience with sorafenib in Child-Pugh B HCC patients. A database of patients with advanced HCC treated with sorafenib was retrospectively evaluated. The median overall survival of Child-Pugh B patients (n=20) was 2.53 months [95% confidence interval (CI): 0.33-5.92 months] and of Child-Pugh A patients (n=100) 9.71 months (95% CI: 6.22-13.04). Child-Pugh B patients had a significantly poorer survival compared to Child-Pugh A patients (P=0.002). The toxicities were similar between the two groups. Metastasis, vascular invasion and alpha-fetoprotein level >1,030 ng/ml were not associated with survival among Child-Pugh B patients (P=0.281, 0.189 and 0.996, respectively). Although the survival outcomes were worse in Child-Pugh B patients treated with sorafenib, the toxicity profile was manageable. Therefore, there remains the question of whether to treat this subgroup of patients and more data are required to define the role of sorafenib in the context of liver dysfunction.
- Neoadjuvant and adjuvant systemic treatment for hepatocellular carcinoma(2021) MATHIAS-MACHADO, Maria Cecilia; FONSECA, Leonardo G. daHepatocellular carcinoma (HCC) is a highly lethal malignancy, and few patients are candidates for curative-intended therapies. The mainstay of curative treatment in HCC is surgical resection, ablation, and transplantation. However, rates of recurrence are high, and there is no established approach to reduce the risk of recurrence and mortality. We discuss the available data and current landscape of (neo)adjuvant therapies aimed at decreasing recurrence risk and improving overall survival, including liver-directed therapies, tyrosine kinase inhibitors, and immunotherapy. Neoadjuvant strategies aimed at downstaging advanced HCC to enable local treatment and minimize the risk of recurrence using novel agents are also a topic of interest in current research. The improvements achieved in the advanced stages with immune-checkpoint inhibitors are priming ongoing trials that address potential future directions for both adjuvant and neoadjuvant strategies that may change the treatment paradigm of HCC in the near future.
- Tyrosine Kinase Inhibitors and Hepatocellular Carcinoma(2020) FONSECA, Leonardo G. da; REIG, Maria; BRUIX, Jordi
- Liver decompensation is a frequent cause of treatment discontinuation and prognostic factor in intermediate-advanced HCC(2023) PINEROA, Federico; ANDERS, Margarita; BERMUDEZ, Carla; DEMIRDJIAN, Ezequiel; VARON, Adriana; PALAZZO, Ana; RODRIGUEZ, Jorge; BELTRAN, Oscar; FONSECA, Leonardo Gomes da; RIDRUEJO, Ezequiel; CABALLINI, Pablo; TAMAGNONE, Norberto; REGGIARDO, Virginia; CHEINQUER, Hugo; ARAUJO, Alexandre; ARUFE, Diego; MARIN, Juan Ignacio; RATUSNU, Natalia; MANERO, Estela; PEREZ, Daniela; VILLA, Marina; OROZCO, Federico; MURGA, Dolores; MARCIANO, Sebastian; BESSONE, Fernando; SILVA, Marcelo; MENDIZABAL, ManuelIntroduction and Objectives: With the advent of new therapeutic options for patients with hepatocellular car-cinoma (HCC) for intermediate or advanced stages of the Barcelona Clinic Liver Cancer (BCLC), regional real -world data regarding prognostic survival factors are of significant importance. Patients and Methods: A multicenter prospective cohort study was conducted in Latin America including BCLC B or C patients since 15th May 2018. We report here the second interim analysis focusing on prognostic varia-bles and causes of treatment discontinuation. Cox proportional hazard survival analysis was performed, esti-mating hazard ratios (HR) and 95% confidence intervals (95% CI). Results: Overall, 390 patients were included, 55.1% and 44.9% were BCLC B and C at the time of study enroll-ment. Cirrhosis was present in 89.5% of the cohort. Among the BCLC-B group, 42.3% were treated with TACE with a median survival since the first session of 41.9 months. Liver decompensation before TACE was inde-pendently associated with increased mortality [HR 3.22 (CI 1.64;6.33); P<.001]. Systemic treatment was initi-ated in 48.2% of the cohort (n=188), with a median survival of 15.7 months. Of these, 48.9% presented first -line treatment discontinuation (44.4% tumor progression, 29.3% liver decompensation, 18.5% symptomatic deterioration, and 7.8% intolerance), and only 28.7% received second-line systemic treatments. Liver decom-pensation [HR 2.9 (1.64;5.29); P<.0001], and symptomatic progression [HR 3.9 (1.53;9.78); P=0.004] were independently associated with mortality after first-line systemic treatment discontinuation. Conclusions: The complexity of these patients, with one-third presenting liver decompensation after systemic therapies, underlines the need for multidisciplinary team management and the central role of hepatologists. (c) 2023 Fundacion Clinica Medica Sur, A.C.
- Combination approaches in hepatocellular carcinoma: How systemic treatment can benefit candidates to locoregional modalities(2022) FONSECA, Leonardo Gomes da; ARAUJO, Raphael L. C.The management of hepatocellular carcinoma (HCC) is challenging because most patients have underlying cirrhosis, and the treatment provides, historically, a limited impact on the natural history of patients with advanced-stage disease. Additionally, recurrence rates are high for those patients who receive local and locoregional modalities, such as surgical (resection and transplantation) or image-guided (ablation and intra-arterial) therapies. Translational research has led to new concepts that are reshaping the current clinical practice. Substantial advancements were achieved in the understanding of the hallmarks that drive hepatocarcinogenesis. This has primed a successful incorporation of novel agents with different targets, such as anti-angiogenic drugs, targeted-therapies, and immune-checkpoint inhibitors. Although clinical trials have proven efficacy of systemic agents in advanced stage disease, there is no conclusive evidence to support their use in combination with loco-regional therapy. While novel local modalities are being incorporated (e.g., radioembolization, microwave ablation, and irreversible electroporation), emerging data indicate that locoregional treatments may induce tumor microenvironment changes, such as hyperexpression of growth factors, release of tumor antigens, infiltration of cytotoxic lymphocytes, and modulation of adaptative and innate immune response. Past trials that evaluated the use of antiangiogenic drugs in the adjuvant setting after ablation or chemoembolization fail to demonstrate a substantial improvement. Current efforts are directed to investigate the role of immunotherapy-based regimens in this context. The present review aims to describe the current landscape of systemic and locoregional treatments for HCC, present evidence to support combination approaches, and address future perspectives.
- Immunotherapy-Based Treatments of Hepatocellular Carcinoma: AJR Expert Panel Narrative Review(2022) CANNELLA, Roberto; LEWIS, Sara; FONSECA, Leonardo da; RONOT, Maxime; RIMOLA, JordiThe advent of immunotherapy for patients with hepatocellular carcinoma (HCC) has changed the treatment landscape and conferred a survival benefit on patients with advanced HCC, who typically have a very poor prognosis. The most pronounced improvements in response, as documented by standardized response criteria based on CT or MRI, have been achieved when immunotherapy is combined with other systemic or locoregional therapies. Immune checkpoint inhibitor treatments result in unique patterns on CT and MRI that challenge the application of conventional response criteria such as RECIST, modified RECIST, and European Association for the Study of the Liver criteria. Thus, newer criteria have been developed to gauge therapy response or disease progression for patients receiving immunotherapy, including immune-related RECIST (iRECIST) and immune-modified RECIST (imRECIST), though these remain unvalidated. In this review, we describe the current landscape of immunotherapeutic agents used for HCC, summarize the results of published studies, review the pathobiologic mechanisms that provide a rationale for the use of these agents, and report on the status of response assessment for immunotherapy either alone or in combination with other treatment options. Finally, consensus statements are provided to inform radiologists about essential considerations in the era of a rapidly changing treatment paradigm for patients with HCC.
- A multidisciplinary approach to peritoneal metastasis from hepatocellular carcinoma: clinical features, management and outcomes(2022) FONSECA, Leonardo G. Da; LEONARDI, Paulo C.; HASHIZUME, Pedro H.; SANSONE, Francesco; SAUD, Lisa R.; CARRILHO, Flair J.; HERMAN, PauloAim of the study: Hepatocellular carcinoma (HCC) is a lethal malignancy with heterogeneous behavior determined by liver function, clinical presentation and treatment response. Peritoneal metastasis (PM) from HCC is rare and management is challenging. We aim to report a cohort of patients with advanced HCC and describe demographic characteristics, treatment and outcomes of patients with PM. Material and methods: We analyzed data from a retrospective cohort of patients with HCC. Patients with PM were analyzed individually. Baseline characteristics, treatment strategy and median overall survival (OS) with 95% confidence interval (CI) were reported. Results: 238 patients with advanced HCC were evaluated. Eleven patients had PM: 7 patients were treated with systemic treatment and 4 were treated with upfront peritonectomy followed by systemic treatment at recurrence. These 4 patients had well-preserved liver function and low disease burden and were younger compared to the total cohort. The median time to recurrence after peritonectomy was 30.25 months (interquartile range [IQR]: 13.53-46.92): 3 of them presented peritoneal recurrence (2 with diffuse peritoneal spread and 1 with concomitant hepatic recurrence) and 1 presented pulmonary recurrence. Overall, patients with PM showed similar OS compared to patients with other metastatic sites (11.8 months; 95% CI: 1.5-19.8 vs. 8 months; 95% CI: 6.7-10, p = 0.901). Patients with PM treated with upfront surgery had a median OS of 60 months (95% CI: 16.7-not reached). Conclusions: Resection of PM from HCC may provide long-term survival in selected patients. A multidisciplinary approach is the optimal strategy for managing PM from HCC.
- Current landscape and future directions for systemic treatments of hepatocellular carcinoma(2023) FONSECA, Leonardo G.; CARRILHO, Flair J.